Feasibility Study of Pemetrexed in Combination With Cisplatin or Carboplatin as Adjuvant Treatment of Non-Small Cell Lung Cancer

• Grade III/IV Adverse Events [ Time Frame: every 21-day cycle for 4 cycles ] [ Designated as safety issue: Yes ]
  Number of patients experiencing Grade III/IV hematologic and non-hematologic adverse events possibly related to study drug or protocol procedures in this study.
• Overall Survival at 3 Years [ Time Frame: baseline to date of death from any cause, assessed at 3 years ] [ Designated as safety issue: Yes ]
  For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year survival rate. Results are presented as probability (%) of survival at 3 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date.
• 3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years [ Time Frame: length of time disease free, assessed at 3 years ] [ Designated as safety issue: No ]
  For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year disease-free rate. Disease-free survival is defined as the time from enrollment to the first observation of disease progression, or death due to any cause. For participants not known to have died and to have had recurrent disease, disease-free survival was censored at the date of the last participant contact with No Recurrence status. Results are presented as probability (%) of disease-free survival at 3 years.
• Overall Survival at 6 Years [ Time Frame: baseline to date of death from any cause, assessed up to 6 years after the last participant was randomized ] [ Designated as safety issue: Yes ]
  For each treatment arm, the Kaplan-Meier technique was used to estimate the 6 year survival rate. Results are presented as probability (%) of survival at 6 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date.

• To characterize the quantitative and qualitative potential toxicities and the necessity of dose reductions and cycle delays due to toxicities of either treatment arm.
• To assess time to event efficacy parameters in both treatment arms including
• Overall survival (assessed after 3 years).
• 3 year disease free survival.
• To assess biomarkers relevant to pemetrexed and disease state and their correlation to clinical outcome (including overall survival, 3 year disease free survival and toxicity).

This study is a multicenter, open-label, two-arm, randomized, parallel Phase 2 feasibility study of pemetrexed in combination with either cisplatin (Arm A) or carboplatin (Arm B) as adjuvant combination-chemotherapy in patients with completely resected, stage Ib or IIa/IIb non-small cell lung cancer (NSCLC).

A two-stage design will be employed independently for both treatment arms, with the possibility of stopping each treatment early for lack of feasibility.

• Drug: pemetrexed
  500 mg/m^2, intravenous (IV), every 21 days x 4 cycles
  Other Names:

  • LY231514
  • Alimta
• Drug: cisplatin
  75 mg/m^2, intravenous (IV), every 21 days x 4 cycles
• Drug: carboplatin
  area under the curve (AUC) 5 mg/ml*min, intravenous (IV), every 21 days x 4 cycles

• Experimental: A: Pemetrexed + Cisplatin
  Interventions:

  • Drug: pemetrexed
  • Drug: cisplatin
• Experimental: B: Pemetrexed + Carboplatin
  Interventions:

  • Drug: pemetrexed
  • Drug: carboplatin

Inclusion Criteria:

• Histologically proven non-small cell lung cancer stage Ib, IIa or IIb
• Must have complete tumor resection by pneumonectomy or lobectomy
• Must have been surgically proven to be N2 negative

Exclusion Criteria:

• Serious concomitant systemic disorder
• Post-operative complications or other surgery related conditions
• A prior malignancy other than NSCLC unless that malignancy was diagnosed and treated at leat 5 years ago.